Toxicity study of continuous administration of physostigmine salicylate

The present study demonstrates that continuous administration with physostigmine salicylate (0.12 or 0.24 mg/kg/hr via mini-osmotic pumps) induces toxicities (e.g., body weight loss, decreased water consumption, tremors, decreased body temperatures, mortality) in guinea pigs. Both blood and brain cholinesterase activity is inhibited dose-dependently by physostigmine salicylate. The signs of toxicity in the guinea pigs which received the low dose appeared within 2 or 3 days and then the animals recovered, while toxic signs in the guinea pigs treated with the high dose of the drug persisted throughout the experiments. The study further shows that continuous administration of physostigmine salicylate also caused down-regulation of muscarinic receptors in the striata of the guinea pigs.